Project Summary Zoonotic diseases present unique challenges for public health due to the complex interactions between humans, animals, pathogens, and the environment. Urbanization, migration, and the urban landscape add additional layers of complexity to these interactions, and the control and prevention of zoonotic pathogens requires innovative multidisciplinary methodological approaches that take into account social, spatial and population dynamics in urban areas. Epidemics of zoonotic pathogens are ongoing in major urban centers across Latin America and worldwide, and among them, the city of Arequipa, Peru is in the midst of a canine rabies epidemic. The drivers of this epidemic work at many levels: Individual- and community-level factors, including social determinants, may explain the currently low vaccination rate of domestic animals against rabies. Urban geography can also affect participation in zoonotic disease control programs, facilitating the emergence of canine rabies and complicating its control. Free-roaming owned and stray dogs with their unique ecology and population dynamics could also impact the results of control activities. In this proposal I will develop a new approach for the control and prevention of zoonotic disease in cities that integrates mathematical and social approaches, using rabies as a model zoonotic disease strongly determined by urban dynamics. Following the urban re-emergence after 15 years, the Ministry of Health has failed to quell the rabies epidemic in Arequipa's complex urban environment. I hypothesize that the failure is due primarily to three factors: 1) Poorly understood determinants of canine vaccination uptake; 2) Ignored spatial heterogeneity of unvaccinated dogs, especially stray dogs; and, 3) Suboptimal placement of vaccine tents across the urban landscape. Under a first aim, a qualitative study and a survey are proposed to identify social and spatial determinants of canine vaccination uptake in urban settings. The second aim will evaluate mathematically different strategies that consider the role of stray dogs in rabies control programs. Finally, the third aim will incorporate social and spatial factors into a mathematical algorithm to optimize the location of vaccine tents. For this third study, a discrete-choice experiment will be performed to test the acceptability of the optimized vaccine stand placements. This proposal aims to produce an urgently needed novel approach for zoonotic disease control programs in cities to integrate urban landscapes, health behaviors, diverse populations, and optimal placement of health service facilities.